Yong Du

Investigation into tautomeric polymorphism of 2-thiobarbituric acid using experimental vibrational spectroscopy combined with DFT theoretical simulation

Vibrational modes of 2-thiobarbituric acid (TBA) tautomeric polymorphs (form I, II and IV) were characterized by terahertz time-domain spectroscopy (THz-TDS) and Raman spectral techniques. The experimental results indicate that both vibrational spectroscopy techniques could be used to recognize the above TBA three tautomeric forms clearly. Experimental THz spectral results show that each of TBA tautomeric polymorphs has distinctive fingerprint peaks in the terahertz region. Raman spectra also show similar results about differences of TBA tautomeric polymorphs, but not significant as that of terahertz spectra since Raman-active vibrational modes are mostly from intra-molecular interaction of various functional groups within the specific molecule while that of terahertz region is more sensitive to inter-molecular interaction within crystalline unit cells. In addition, density functional theory (DFT) was used to simulate the optimized structures and vibrational modes of these three TBA tautomeric forms above. The characteristic vibrational modes of TBA polymorphs are assigned comparing the simulated DFT results with experimental vibrational spectra. The results provide fundamental benchmark for the study of pharmaceutical polymorphism based on both Raman and terahertz vibrational spectroscopic techniques combined with theoretical simulations.

Investigation of thermal denaturation of solid oxytocin by terahertz dielectric spectroscopy

We investigate the thermal denaturation of solid oxytocin using terahertz time domain spectroscopy(THz-TDS). When the peptide is heated up from 25°C to 107°C and cooled down to 25°C again, an irreversible decrease in its THz absorption coefficient and refractive index is observed. The corresponding frequency-dependent permittivity during heating is fitted by the Debye model with single relaxation time. The relaxation times during temperature rising agree very well with Arrhenius equation with the activation energy of 3.12kJ/(K•mol) as an indicator for its thermal denaturation difficulty.

Characteristics of chiral and racemic ketoprofen drugs using terahertz time-domain spectroscopy

Absorption spectra of chiral S-(+)- and racemic RS-ketoprofen pharmaceutical molecules in crystalline form were recorded in the terahertz region between 6 and 66 cm-1 (0.2 ~ 2.0 THz) by using time-domain terahertz spectroscopic (THz-TDS) measurement. Different distinctive absorption features were observed which are strikingly sensitive to the change of subtle conformational structures within such isostructural crystal molecules. The results suggest that the THz-TDS technique can be definitely used for distinguishing between chiral and racemic compounds in pharmaceutical and biological fields.

Terahertz spectral study of L- and DL-fudosteine

We have studied the absorption spectral of L-and DL-fudosteine using terahertz time-domain spectroscopy (THz-TDS) at room temperature. The results show that both of them have unique absorption fingerprint peaks in terahertz range and can be identified by these peaks. The absorption spectrum of the fudosteine capsule has also been studied. Its absorption spectrum is similar to that of L-fudosteine. Thus, it proves that the main component of fudosteine capsule is L-fudosteine. The study indicates that THz-TDS technology is a new method to identify and analyze main components of material.

Investigating the position isomerism effect of dihydroxybenzoic acid compounds by terahertz time-domain spectroscopy

Far-infrared vibrational absorption of a series of dihydroxybenzoic acid (DHBA) compounds with different substituted hydroxy group at different positions have been investigated using terahertz time-domain spectroscopy (THz-TDS) at room temperature. The experimental results show large difference among absorption spectra of different DHBA (2,3-DHBA, 2,4-DHBA, 2,5-DHBA, 2,6-DHBA) compounds in 0.2 ~ 2.0 THz region, which probably originated from the difference of intra-molecular and inter-molecular hydrogen bonds due to the presence of two hydroxyl group in different positions with respect to the carboxylic group in different DHBAs. All the experimental DHBAs vibrational modes showed distinct fingerprint absorption in THz region and theorectical calculation based on density functional theory (DFT) was carried out to assist the analysis and assignment of the vibrational modes. The results indicate that THz-TDS technology can not only give a new experimental method to identify and characterize the position isomerism effect of hydroxyl group between such different kinds of DHBAs from molecule-level, but also provide a useful suggestion for further assessing the possible relationships between the DHBAs vibrational properties and the effects of the substituted hydroxy group position to better know their biochemical activities in food, pharmaceutical and cosmetic fields.

Conformational characteristics of chiral and racemic naproxen molecules investigated by terahertz time-domain spectroscopy

Absorption spectra in the terahertz region between 6 and 66 cm-1 (0.2 ~ 2.0 THz) were measured for S-(+)-, R-(-) and RS-naproxen pharmaceutical molecules in crystalline form using time-domain terahertz spectroscopic (THz-TDS) technique at room temperature. Different absorption features were observed for the racemic RS-naproxen and its corresponding enantiomers (S-(+)- and R-(-)-naproxen). The observed THz absorption bands are strikingly sensitive to the change of subtle conformational structures despite that the isostructurality exists within such crystal molecules. The results show that the THz-TDS technique can be definitely used for distinguishing between chiral and racemic compounds in pharmaceutical and biological fields.

Thermal denaturation of protein studied by terahertz time-domain spectroscopy

In this study, the absorption spectra of native or thermal protein were measured in 0.2-1.4THz using terahertz time-domain spectroscopy (THz-TDS) system at room temperature, their absorption spectra and the refractive spectra were obtained. Experimental results indicate that protein both has strong absorption but their characteristics were not distinct in the THz region, and the absorption decreased during thermal denatured state. In order to prove protein had been denatured, we used Differential scanning calorimeter (DSC) measured their denatured temperature, from their DSC heating traces, collagen Td=101℃, Bovine serum albumin Td=97℃. While we also combined the Fourier transform infrared spectrometer (FTIR) to investigate their secondary and tertiary structure before and after denatuation, but the results did not have the distinct changes. We turned the absorption spectra and the refractive spectra to the dielectric spectra, and used the one-stage Debye model simulated the terahertz dielectric spectra of protein before and after denaturation. This research proved that the terahertz spectrum technology is feasible in testing protein that were affected by temperature or other factors，which can provide theoretical foundation in the further study about the THz spectrum of protein and peptide temperature stability.